血清游离miRNA-132及miRNA-301a水平与妊娠期糖尿病相关性研究
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摘要
目的探讨妊娠期糖尿病孕妇血清miRNA-132及miRNA-301a水平与机体炎症调节状态及胰岛素抵抗的关系。方法选取2017年3月～2018年2月在我院产检并分娩的30例确诊为GDM的孕妇为实验组(GDM组),另30例健康孕妇为对照组,比较两组孕24～28周空腹血糖、空腹胰岛素及炎症因子相关指标水平;采用q-PCR方法检测血清mi RNA-132及miRNA-301a的表达水平,对比分析两组之间的差异及血清mi RNA-132及miRNA-301a水平相关因素。结果两组研究对象年龄及血清mi RNA-132水平比较,差异无统计学意义(P> 0.05);GDM组孕妇BMI及、HOMA-IR指数及血清中FPG、FINS、IL-1、IL-6、TNF-α、CRP、miRNA-301a水平均明显高于对照组,差异有统计学意义(P <0.05),而血清IL-10水平低于对照组孕妇(P <0.05);血清miRNA-301a水平与年龄、BMI无明显相关性(P> 0.05),而与血清FBG、FINS、IL-1、IL-6、TNF-α及CRP水平和HOMA-IR指数呈正相关(r=0.2614、0.3538、0.5025、0.3017、0.1947、0.1435、0.5439,P <0.05),与血清IL-10水平呈负相关(r=-0.1856,P <0.05);而血清游离miRNA-132水平与观察项目均无明显相关性(P> 0.05)。结论 miRNA-301a的异常表达与GDM的发生发展有关,其可能通过调节机体抗炎-促炎失衡从而引起GDM发生,可能成为预测和治疗GDM的重要靶点。
Objective To investigate the relationship between serum miRNA-132 and miRNA-301 a levels in pregnant women with gestational diabetes mellitus(GDM) and the state of inflammation regulation and insulin resistance. Methods 30 pregnant women with GDM in Yangxin Maternity and Child Care Hospital from March2017 to February 2018 were selected as experimental group(GDM group),another 30 healthy pregnant women were selected as the control group.The levels of fasting blood glucose,fasting insulin and inflammatory factors were compared between the two groups at 24 to 28 weeks' gestation.The expression levels of serum miRNA-132 and miRNA-301 a were detected by q-PCR.The differences between the two groups and the related factors of serum miRNA-132 and miRNA-301 a levels were compared and analyzed. Results There were no significantly differences in age and serum miRNA-301 a levels between the two groups(all P > 0.05).BMI,HOMA-IR index,FINS,IL-1,IL-6,TNF-α,CRP,miRNA-301 a in the GDM group were significantly higher than those in the control group,but serum IL-10 level was lower than that of the control group(all P < 0.05).Serum miRNA-301 a level had no significant correlation with age and BMI(all P > 0.05),while positively correlated with serum FBG,FINS,IL-1,IL-6,TNF-α,CRP level and HOMA-IR index(r=0.2614,0.3538, 0.5025,0.3017,0.1947,0.1435,0.5439,respe ctively,all P < 0.05),and negatively correlated with serum il-10 level(r=-0.1856,P < 0.05).However,there was no significant correlation between the level of serum free miRNA-132 and the observation items(P > 0.05). Conclusion The abnormal expression of miRNA-301 a is related to the occurrence and development of GDM,which may cause the occurrence of GDM by regulating the imbalance between anti-inflammatory and proinflammatory,and may be an important target for the prediction and treatment of GDM.
Objective To investigate the relationship between serum miRNA-132 and miRNA-301 a levels in pregnant women with gestational diabetes mellitus(GDM) and the state of inflammation regulation and insulin resistance. Methods 30 pregnant women with GDM in Yangxin Maternity and Child Care Hospital from March2017 to February 2018 were selected as experimental group(GDM group),another 30 healthy pregnant women were selected as the control group.The levels of fasting blood glucose,fasting insulin and inflammatory factors were compared between the two groups at 24 to 28 weeks' gestation.The expression levels of serum miRNA-132 and miRNA-301 a were detected by q-PCR.The differences between the two groups and the related factors of serum miRNA-132 and miRNA-301 a levels were compared and analyzed. Results There were no significantly differences in age and serum miRNA-301 a levels between the two groups(all P > 0.05).BMI,HOMA-IR index,FINS,IL-1,IL-6,TNF-α,CRP,miRNA-301 a in the GDM group were significantly higher than those in the control group,but serum IL-10 level was lower than that of the control group(all P < 0.05).Serum miRNA-301 a level had no significant correlation with age and BMI(all P > 0.05),while positively correlated with serum FBG,FINS,IL-1,IL-6,TNF-α,CRP level and HOMA-IR index(r=0.2614,0.3538, 0.5025,0.3017,0.1947,0.1435,0.5439,respe ctively,all P < 0.05),and negatively correlated with serum il-10 level(r=-0.1856,P < 0.05).However,there was no significant correlation between the level of serum free miRNA-132 and the observation items(P > 0.05). Conclusion The abnormal expression of miRNA-301 a is related to the occurrence and development of GDM,which may cause the occurrence of GDM by regulating the imbalance between anti-inflammatory and proinflammatory,and may be an important target for the prediction and treatment of GDM.
引文
[1]张宏秀,陈文玮,孙丽洲.妊娠期糖尿病胰岛素抵抗的研究进展[J].中国妇产科临床杂志,2011,12(2):154-156.
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[5]胡春玲,罗毅平,李莉群,等.妊娠糖尿病与炎症因子关系的研究[J].南昌大学学报(医学版),2006,46(2):62-64.
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[8]彭海燕,李华萍.微小RNA在妊娠期糖尿病及妊娠结局中的作用[J].中国糖尿病杂志,2017,9(11):723-725.
[9]Li M,Shao H,Zhang X,et al.Hesperidin alleviates lipopolysaccharide-induced neuroinflammation in mice by promoting the miRNA-132 pathway[J].Inflammation,2016,39(5):1681-1689.
[10]Huang L,Liu Y,Wang L,et al.Down-regulation of miR-301a suppresses pro-inflammatory cytokines in Toll-like receptor-triggered macrophages[J].Immunology,2013,140(3):314-322.
[11]Zhu W,Yang H,Wei Y,et al.Comparing the diagnostic criteria for gestational diabetes mellitus of World Health Organization 2013 with 1999 in Chinese population[J].Chin Med J(Engl),2015,128(1):125-127.
[12]Abell SK,Court D,Boyle JA,et al.Inflammatory and other biomarkers:role in pathophysiology and prediction of gestational diabetes mellitus[J].Int J Mol Sci,2015,16(6):13442-13473.
[13]Ma X,Yan F,Deng Q,et al.Modulation of tumorigenesis by the pro-inflammatory microRNA miR-301a in mouse models of lung cancer and colorectal cancer[J].Cell Discov,2015,1:15005.
[14]周培,丛林,袁静.核转录因子-κB与妊娠期糖尿病发病机制的研究[J].实用妇产科杂志,2017,33(3):189-193.
[15]李松,丛林,袁静,等.TLR4乙酰化对LPS-TLR4-NF-κB通路的影响及其在妊娠期糖尿病发病机制中的作用[J].安徽医科大学学报,2016,51(1):26-30.
[16]陈蔓,刘虹,刘艳,等.妊娠期糖尿病孕妇外周血及胎盘组织NF-κB表达与胰岛素抵抗的相关性研究[J].中国妇幼保健,2014,29(1):134-136.
[17]Pérez-Pérez A,Guadix P,MaymóJ,et al.Insulin and Leptin Signaling in Placenta from Gestational Diabetic Subjects[J].Horm Metab Res,2016,48(1):62-69.
[18]Nayar G,Gauna A,Chukkapalli S,et al.Polymicrobial infection alter inflammatory microRNA in rat salivary glands during periodontal disease[J].Anaerobe,2016,38:70-75.
[19]Huang X,Qi L,Lu W,et al.miRNA-301a induces apoptosis of chronic myelogenous leukemia cells by directly targeting TIMP2/ERK1/2 and AKT pathways[J].Oncol Rep,2017,37(2):945-952.
[20]Lannes J,L'H?te D,Garrel G,et al.Rapid communication:A microRNA-132/212 pathway mediates GnRH activation of FSH expression[J].Mol Endocrinol,2015,29(3):364-372.
[21]宋荣华,许文灿,傅玉才.SIRT1与糖尿病[J].广东医学,2010,31(20):2717-2719.
[22]梁冬儒,张红花,陈晓玲.妊娠期显性糖尿病和妊娠期糖尿病患者在妊娠晚期临床特征差异[J].中国医药科学,2017,7(24):107-109.
[23]罗莉,陈莉.妊娠期糖尿病孕妇围生期母婴结局分析[J].中国现代医生,2017,55(36):58-60.
[24]周婧君,陈海萍.门冬胰岛素治疗妊娠期糖尿病的效果及其对患者血清氧化物质水平的影响分析[J].中国当代医药,2017,24(36):69-71.
[2]Alfadhli EM.Gestational diabetes mellitus[J].Saudi Med J,2015,36(4):399-406.
[3]Lekva T1,Norwitz ER,Aukrust P,et al.Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus[J].Curr Diab Rep,2016,16(4):26.
[4]Pantham P,Aye IL,Powell TL,et al.Inflammation in maternal obesity and gestational diabetes mellitus[J].Placenta,2015,36(7):709-715.
[5]胡春玲,罗毅平,李莉群,等.妊娠糖尿病与炎症因子关系的研究[J].南昌大学学报(医学版),2006,46(2):62-64.
[6]余芳,薛耀明,李晨钟,等.血清IL-6、hs-CRP与妊娠期糖尿病胰岛素抵抗的关系[J].南方医科大学学报,2007,27(6):799-801.
[7]Zhao C,Dong J,Jiang T,et al.Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus[J].PLoS One,2011,6(8):e23925.
[8]彭海燕,李华萍.微小RNA在妊娠期糖尿病及妊娠结局中的作用[J].中国糖尿病杂志,2017,9(11):723-725.
[9]Li M,Shao H,Zhang X,et al.Hesperidin alleviates lipopolysaccharide-induced neuroinflammation in mice by promoting the miRNA-132 pathway[J].Inflammation,2016,39(5):1681-1689.
[10]Huang L,Liu Y,Wang L,et al.Down-regulation of miR-301a suppresses pro-inflammatory cytokines in Toll-like receptor-triggered macrophages[J].Immunology,2013,140(3):314-322.
[11]Zhu W,Yang H,Wei Y,et al.Comparing the diagnostic criteria for gestational diabetes mellitus of World Health Organization 2013 with 1999 in Chinese population[J].Chin Med J(Engl),2015,128(1):125-127.
[12]Abell SK,Court D,Boyle JA,et al.Inflammatory and other biomarkers:role in pathophysiology and prediction of gestational diabetes mellitus[J].Int J Mol Sci,2015,16(6):13442-13473.
[13]Ma X,Yan F,Deng Q,et al.Modulation of tumorigenesis by the pro-inflammatory microRNA miR-301a in mouse models of lung cancer and colorectal cancer[J].Cell Discov,2015,1:15005.
[14]周培,丛林,袁静.核转录因子-κB与妊娠期糖尿病发病机制的研究[J].实用妇产科杂志,2017,33(3):189-193.
[15]李松,丛林,袁静,等.TLR4乙酰化对LPS-TLR4-NF-κB通路的影响及其在妊娠期糖尿病发病机制中的作用[J].安徽医科大学学报,2016,51(1):26-30.
[16]陈蔓,刘虹,刘艳,等.妊娠期糖尿病孕妇外周血及胎盘组织NF-κB表达与胰岛素抵抗的相关性研究[J].中国妇幼保健,2014,29(1):134-136.
[17]Pérez-Pérez A,Guadix P,MaymóJ,et al.Insulin and Leptin Signaling in Placenta from Gestational Diabetic Subjects[J].Horm Metab Res,2016,48(1):62-69.
[18]Nayar G,Gauna A,Chukkapalli S,et al.Polymicrobial infection alter inflammatory microRNA in rat salivary glands during periodontal disease[J].Anaerobe,2016,38:70-75.
[19]Huang X,Qi L,Lu W,et al.miRNA-301a induces apoptosis of chronic myelogenous leukemia cells by directly targeting TIMP2/ERK1/2 and AKT pathways[J].Oncol Rep,2017,37(2):945-952.
[20]Lannes J,L'H?te D,Garrel G,et al.Rapid communication:A microRNA-132/212 pathway mediates GnRH activation of FSH expression[J].Mol Endocrinol,2015,29(3):364-372.
[21]宋荣华,许文灿,傅玉才.SIRT1与糖尿病[J].广东医学,2010,31(20):2717-2719.
[22]梁冬儒,张红花,陈晓玲.妊娠期显性糖尿病和妊娠期糖尿病患者在妊娠晚期临床特征差异[J].中国医药科学,2017,7(24):107-109.
[23]罗莉,陈莉.妊娠期糖尿病孕妇围生期母婴结局分析[J].中国现代医生,2017,55(36):58-60.
[24]周婧君,陈海萍.门冬胰岛素治疗妊娠期糖尿病的效果及其对患者血清氧化物质水平的影响分析[J].中国当代医药,2017,24(36):69-71.